rs2990510

chr1-197051528-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001994.3(F13B):c.1556-649A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 151,994 control chromosomes in the GnomAD database, including 5,507 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.26 (5507 hom., cov: 32)
• Consequence: F13B NM_001994.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308

Genes affected

F13B (HGNC:3534): (coagulation factor XIII B chain) This gene encodes coagulation factor XIII B subunit. Coagulation factor XIII is the last zymogen to become activated in the blood coagulation cascade. Plasma factor XIII is a heterotetramer composed of 2 A subunits and 2 B subunits. The A subunits have catalytic function, and the B subunits do not have enzymatic activity and may serve as a plasma carrier molecules. Platelet factor XIII is comprised only of 2 A subunits, which are identical to those of plasma origin. Upon activation by the cleavage of the activation peptide by thrombin and in the presence of calcium ion, the plasma factor XIII dissociates its B subunits and yields the same active enzyme, factor XIIIa, as platelet factor XIII. This enzyme acts as a transglutaminase to catalyze the formation of gamma-glutamyl-epsilon-lysine crosslinking between fibrin molecules, thus stabilizing the fibrin clot. Factor XIII deficiency is classified into two categories: type I deficiency, characterized by the lack of both the A and B subunits; and type II deficiency, characterized by the lack of the A subunit alone. These defects can result in a lifelong bleeding tendency, defective wound healing, and habitual abortion. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
F13B	NM_001994.3	c.1556-649A>C		intron_variant		ENST00000367412.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
F13B	ENST00000367412.2	c.1556-649A>C		intron_variant		1	NM_001994.3	P1
F13B	ENST00000649282.1	c.311-649A>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39350 AN: 151876 Hom.: 5501 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.495

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.259

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.259 AC: 39364 AN: 151994 Hom.: 5507 Cov.: 32 AF XY: 0.257 AC XY: 19073 AN XY: 74282

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.255

Gnomad4 ASJ AF: 0.300

Gnomad4 EAS AF: 0.130

Gnomad4 SAS AF: 0.297

Gnomad4 FIN AF: 0.306

Gnomad4 NFE AF: 0.316

Gnomad4 OTH AF: 0.264

Alfa AF: 0.321 Hom.: 7004

Bravo AF: 0.251

Asia WGS AF: 0.222 AC: 770 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	5.9
Dann	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2990510; hg19: chr1-197020658;